Early detection of neoplastic changes in the oral cavity holds great promise for improving survival rates and the quality of life of survivors. The high spatial resolution of optical imaging could make possible the diagnosis of neoplastic lesions while they are still in the submillimeter range in size and highly treatable. Both biochemical and morphological changes accompany the transition from normal tissue to neoplastic tissue. Yet the optical techniques heretofore investigated as potential screening and diagnostic tools for cancer have largely concentrated on detecting one or the other, principally because of the fundamental lack of optical imaging modalities which readily provide both types of information. Here we propose to simultaneously collect morphological and biochemical information by combining two well developed optical imaging techniques, optical coherence tomography (OCT) and fluorescence lifetime imaging (FLIM). Since OCT and FLIM measure different tissue characteristics (structural and biochemical, respectively), we hypothesize that their synergy will increase the sensitivity and specificity for detecting early epithelial cancer, compared to each modality applied independently. The ultimate goal of this line of research is to develop a novel optical imaging system and associated algorithms for noninvasive optical biopsy in oral cancer. Such a system may serve as a diagnostic and monitoring tool, a screening tool, a guide to standard biopsy and surgical intervention, and a tool for quantitative evaluation of therapeutic response. While this proposal is focused on the early detection of oral cancer we believe that the system and algorithms developed will also be generally applicable to many of the cancers of the epithelium. The following three specific aims will be addressed in this proposal: Aim 1: To develop a novel optical multimodality imaging system by combining OCT and FLIM technology for simultaneous micro-anatomical and biochemical imaging of tissue in vivo and ex vivo. Aim 2: To acquire a unique database of OCT/FLIM images and corresponding histopathology of the development of oral cancer in a hamster cheek pouch model. Aim 3: To develop new computational methods for OCT/FLIM image analysis and evaluate the sensitivity/specificity of the proposed multimodality imaging system for the early detection of oral neoplasia. The successful completion of this work will demonstrate the potential of combining OCT and FLIM as a means for non-invasive optical detection of oral pre-malignant and malignant lesions. PUBLIC HEALTH RELEVANCE: Early detection of epithelial oral cancer could significantly reduce cancer morbidity and mortality. Currently, the diagnosis of oral epithelial cancers is performed through direct or endoscopic visual inspection followed by biopsy. Since visual inspection is subjective and early pre-cancers are often not detectable under visual inspection, multiple biopsies have to be taken to increase the likelihood of finding a cancerous lesion. Therefore, techniques that can diagnose oral epithelial pre-cancer and cancer with higher accuracy than visual inspection alone are needed to guide tissue biopsy. Optical imaging is particularly well suited for imaging many of the epithelial tissues of the body including the oral cavity. Both biochemical and morphological changes accompany the transition from normal tissue to neoplastic tissue, yet the optical techniques heretofore investigated as potential screening and diagnostic tools for cancer have largely concentrated on one or the other. Here we propose to simultaneously collect both morphological and biochemical information by combining two well developed optical imaging techniques, optical coherence tomography (OCT) and fluorescence lifetime imaging (FLIM). The ultimate goal of this line of research is to develop a novel optical imaging system and associated algorithms which will enable noninvasive optical biopsy in oral cancer.